In Science (New York, N.Y.)
Many complex human phenotypes exhibit sex-differentiated characteristics. However, the molecular mechanisms underlying these differences remain largely unknown. We generated a catalog of sex differences in gene expression and in the genetic regulation of gene expression across 44 human tissue sources surveyed by the Genotype-Tissue Expression project (GTEx, v8 release). We demonstrate that sex influences gene expression levels and cellular composition of tissue samples across the human body. A total of 37% of all genes exhibit sex-biased expression in at least one tissue. We identify cis expression quantitative trait loci (eQTLs) with sex-differentiated effects and characterize their cellular origin. By integrating sex-biased eQTLs with genome-wide association study data, we identify 58 gene-trait associations that are driven by genetic regulation of gene expression in a single sex. These findings provide an extensive characterization of sex differences in the human transcriptome and its genetic regulation.
Oliva Meritxell, Muñoz-Aguirre Manuel, Kim-Hellmuth Sarah, Wucher Valentin, Gewirtz Ariel D H, Cotter Daniel J, Parsana Princy, Kasela Silva, Balliu Brunilda, Viñuela Ana, Castel Stephane E, Mohammadi Pejman, Aguet François, Zou Yuxin, Khramtsova Ekaterina A, Skol Andrew D, Garrido-Martín Diego, Reverter Ferran, Brown Andrew, Evans Patrick, Gamazon Eric R, Payne Anthony, Bonazzola Rodrigo, Barbeira Alvaro N, Hamel Andrew R, Martinez-Perez Angel, Soria José Manuel, Pierce Brandon L, Stephens Matthew, Eskin Eleazar, Dermitzakis Emmanouil T, Segrè Ayellet V, Im Hae Kyung, Engelhardt Barbara E, Ardlie Kristin G, Montgomery Stephen B, Battle Alexis J, Lappalainen Tuuli, Guigó Roderic, Stranger Barbara E